Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions. •NTRK gene fusions are oncogenic drivers in a variety of tumor types including adult and pediatric sarcomas.•TRK inhibitors provide effective treatment options for patients with sarcomas harboring NTRK gene fusions.•Integrating NTRK testing into the management of patients with sarcoma is challenging due to the rarity of this biomarker.•Massive parallel RNA sequencing provides the optimal NTRK fusion test and immunohistochemistry is a valuable screening tool.•We propose a diagnostic strategy that considers histologic and molecular subtypes to facilitate routine NTRK fusion testing.